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PubMed1998

Chronic chorioamnionitis: a clinicopathologic and immunohistochemical study.

Lymphocytic inflammation of the fetal membranes is unusual and has been termed chronic chorioamnionitis. We report the clinicopathologic and immunohistochemical findings in 31 placentas with chronic chorioamnionitis. The most common histopathologic association was chronic villitis of unknown etiology, which was identified in 22 (71%) of the 31 placentas. The severity of the chronic villitis did not correlate with the severity of chronic chorioamnionitis. Additional placental findings included chronic intervillositis in two, fetal vessel thrombosis in five, hemorrhagic endovasculitis in four, decidual chronic vasculitis in three, and atherosis in one. Maternal history included pregnancy-induced hypertension in six and diabetes in one. Twelve infants were preterm, and five had intrauterine growth retardation. There was no neonatal sepsis or death. Immunohistochemical staining in areas of chronic chorioamnionitis showed CD3+ and CD8+ cells present in moderate numbers, and CD4+ cells in smaller numbers. CD20+ and CD56+ cells were rare or absent. Chronic chorioamnionitis is commonly associated with chronic villitis of unknown etiology, shares similar clinical associations, and may have a related cause, possibly immunologic.

Adolescent↗

PubMedDate not supplied

Phagocytosis of chorion laeve trophoblasts in patients with chorioamnionitis-associated preterm delivery: ultrastructural and enzyme-histochemical observations.

The purpose of the present study was to examine morphological evidence for the presence of phagocytosing chorion laeve trophoblasts in fetal membranes from patients who had undergone chorioamnionitis-related preterm delivery. Chorion laeve trophoblasts from six patients, who underwent preterm delivery (28-34 weeks of gestation) complicated with chorioamnionitis, were analysed using transmission electron microscopy and ultrastructural enzyme-histochemistry for acid phosphatase, and compared with those from gestational age-matched chorioamnionitis-negative controls. Cytosomal cell projections, phagosomes, phagocytosis of degenerated cells and cell debris, attachment or fusion of lysosomes to the phagosomal membranes and phagosomal membranes positive for acid phosphatase staining were characteristically observed much more frequently in trophoblasts with chorioamnionitis than those without. The results indicated that chorion laeve trophoblasts in fetal membranes from patients having undergone chorioamnionitis-related preterm delivery underwent phagocytosis. Such phagocytosing trophoblasts may play a role in the pathophysiology or pathogenesis of infection-related preterm delivery.

Acid Phosphatase↗

PubMed1996

Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis.

Preterm labor associated with intrauterine infection is characterized by increased amniotic fluid concentrations of various proinflammatory cytokines, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage inflammatory protein-1alpha (MIP-1alpha). The purpose of this study was to determine if preterm labor in women with clinically evident chorioamnionitis is marked by elevations of the anti-inflammatory cytokine interleukin-4 (IL-4) and the T cell growth factor IL-2. Amniotic fluid samples were obtained from (1) women at term, not in labor (n = 10); (2) women at term, in labor (n = 10); (3) women with preterm contractions but undelivered within 1 week of amniotic fluid collection (n = 10); (4) women with preterm labor and delivery without clinically evident chorioamnionitis (n = 10); (5) women with preterm labor associated with chorioamnionitis (n = 8); and (6) women with preterm labor and delivery without infection matched with patients with chorioamnionitis (n = 8). Amniotic fluid concentrations of IL-4 and IL-2 were determined for each sample with a specific and sensitive enzyme-linked immunoassay. We found that women with infection-associated preterm labor and delivery had significantly higher concentrations of IL-4 when compared to appropriately matched controls (p < 0.05). Additionally, women with preterm labor and delivery not associated with infection had higher amniotic fluid IL-4 concentrations than women with preterm contractions but no labor (p < 0.05). Women with term labor had rare modest elevations of amniotic fluid IL-4. No IL-2 was detected in any sample. Our data indicate that amniotic fluid IL-4 is elevated in women with preterm labor and delivery, particularly in association with chorioamnionitis. We suggest that IL-4, although previously considered an anti-inflammatory agent, may have a paradoxical proinflammatory role in the pathogenesis of infection-associated preterm labor.

Adult↗

PubMed1990

Evaluation of potential early markers of chorioamnionitis associated with preterm premature ruptured membranes.

Optimal expectant management of preterm premature rupture of membranes (PROM) requires the early detection of chorioamnionitis. To date, however, no universally sensitive and specific marker for chorioamnionitis has been identified. Recently, the serial determination of plasma fibronectin, antithrombin, and prekallikrein has been reported to facilitate the early detection of sepsis in critically ill neonates and adult surgical patients. A cross-sectional study was undertaken to determine if plasma levels of these markers change significantly in patients with overt chorioamnionitis following expectant management of preterm PROM. Plasma levels of fibronectin and prekallikrein were not significantly different between the study (30 patients with overt chorioamnionitis following preterm PROM) and control (30 undelivered patients without antenatal complication matched for gestational age) groups. Antithrombin levels were significantly lower in the study group (p less than 0.05), but the magnitude of the difference (102% versus 94%) is not likely to be of clinical significance. We conclude that determination of plasma levels of fibronectin, prekallikrein, and antithrombin is not likely to aid in the early detection of chorioamnionitis in the setting of preterm (PROM).

Antithrombins↗

PubMed2002

Physical properties of the chorioamnion throughout gestation.

OBJECTIVE: Our purpose was to assess the tensile strength of the chorioamnion at various gestational ages. STUDY DESIGN: Segments of chorioamnion were obtained from 35 patients delivered at gestational ages ranging from 17 to 41 weeks. Clinical information including gestational age, chorioamnionitis, premature rupture of membranes, and onset of labor was recorded. Tensile strength (grams to burst and deflection at rupture) was measured on 2 to 16 specimens per patient. Tensile strength of several commercial products was used for comparison. RESULTS: Tensile strength increases up to 20 weeks of gestation and then plateaus until 39 weeks of gestation, when it falls dramatically. Clinical chorioamnionitis alone did not affect tensile strength, but gross membrane inflammation resulted in reduced tensile strength. CONCLUSIONS: Tensile strength of the chorioamnion varies with gestational age. This baseline information will be useful in assessing the effects of various conditions and therapies on membrane strength and may provide insight into spontaneous rupture of membranes.

Chorioamnionitis↗

PubMed2003

Neutrophil granule products: can they identify subclinical chorioamnionitis in patients with preterm premature rupture of membranes?

OBJECTIVE: Our purpose was to determine whether maternal plasma levels of neutrophil granule products are elevated in patients with chorioamnionitis after preterm premature rupture of membranes (PROM). STUDY DESIGN: Fifty-two patients between 24 and 34 weeks' gestation with preterm PROM were included. Plasma samples for defensins and lactoferrin were collected throughout latency. Fifty-two control subjects between 26 and 30 weeks' gestation were recruited for baseline levels. RESULTS: Mean control defensin levels were compared with mean defensin levels on admission (668 ng/mL vs 5665 ng/mL, P<.01). Mean defensin levels on admission in patients without chorioamnionitis were compared with those of patients in whom histologic chorioamnionitis developed (520 ng/mL vs 9163 ng/mL, P<.01). The same relationships were not demonstrated for lactoferrin. With use a defensin value of 1500 ng/mL on admission, the sensitivity is 76% and specificity is 94% in predicting histologic chorioamnionitis. CONCLUSIONS: Maternal plasma levels of defensins are markers of histologic chorioamnionitis in patients after preterm PROM.

Anti-Infective Agents↗

PubMed1999

Generation of peroxynitrite and apoptosis in placenta of patients with chorioamnionitis: possible implications in placental abruption.

The reaction of nitric oxide (NO) and superoxide results in the formation of peroxynitrite, a potent and relatively long-lived oxidant. In infectious diseases, these molecules are not only bactericidal but also toxic to host cells. Chorioamnionitis is often complicated by premature rupture of membranes and can be associated with placental abruption. These diseases are significant causes of premature low-birth-weight deliveries and consequently the morbidity and mortality of neonates. Lipopolysaccharide, bacterial endotoxin, is known to be elevated in the amniotic fluid of patients with chorioamnionitis. Lipopolysaccharide is known to induce the formation of NO and superoxide. We report here that nitrite/nitrate, stable metabolites of NO, were increased in serum from patients with chorioamnionitis. Immunohistochemical studies demonstrated enhanced expression of inducible NO synthase and formation of nitrotyrosine, a footprint of peroxynitrite, in the placentae from patients with chorioamnionitis and also in patients with placental abruption. Furthermore, apoptotic cell death was also increased in the placentae from patients with both diseases. These results suggest that chorioamnionitis and a portion of placental abruption may share a common cascade of placental injury. Nitric oxide and its metabolities may play an important role in this cascade.

Adult↗

PubMed2004

Chorioamnionitis increases matrix metalloproteinase-8 concentrations in bronchoalveolar lavage fluid from preterm babies.

OBJECTIVE: To determine the effects of chorioamnionitis and antenatal corticosteroids on matrix metalloproteinase-8 (MMP-8) concentrations in bronchoalveolar lavage (BAL) fluid from preterm babies in the first week of life. DESIGN: Prospective observational study. SETTING: Regional neonatal intensive care unit. PATIENTS: Thirty five ventilated preterm babies < 33 weeks gestation, seven of whom were born after chorioamnionitis, which was diagnosed histologically as the presence of inflammatory cells in the chorioamnionic plate. METHODS: MMP-8 was measured by enzyme linked immunosorbent assay (ELISA) in 90 serial BAL samples taken during the first six postnatal days. The median MMP-8 concentration for each baby was calculated. RESULTS: Median MMP-8 concentrations were higher in the chorioamnionitis group than in those without (43 v 5 ng/ml). Partial or complete courses of antenatal corticosteroids had no effect on MMP-8 concentrations. CONCLUSIONS: Higher concentrations of MMP-8 are found in BAL fluid from preterm babies from pregnancies complicated by chorioamnionitis. This type I collagenase may contribute to the lung injury that occurs in some babies with respiratory distress syndrome.

Adrenal Cortex Hormones↗

PubMed2005

Interleukin-6 and interleukin-8 are elevated in the cerebrospinal fluid of infants exposed to chorioamnionitis.

BACKGROUND: The clinical or histologic diagnosis of chorioamnionitis has been associated with an increased risk of neuropathology and adverse neurologic outcomes in premature and term infants. Inflammatory cytokines have been implicated in the pathogenesis of these processes. The objective of this study was to determine whether exposure to chorioamnionitis and fetal inflammatory syndrome is associated with elevated concentrations of inflammatory cytokines (TNF-alpha, IL-6, and IL-8) in the CSF of term and preterm infants. METHODS: Eighty-four mother/infant pairs were studied, 54 infants were premature. Twenty-eight showed signs of maternal (n = 14), or fetal (n = 14) inflammation based on placental pathology; mothers of 24 infants showed signs of clinical chorioamnionitis not confirmed by placental pathology and 32 infants were considered as 'controls' since they had only transient difficulty adjusting to extra-uterine life warranting evaluation for sepsis. The cytokine concentrations in the CSF were measured within 24 h of birth. RESULTS: When compared to the control group (IL-8 = 341 +/- 170 pg/ml and IL-6 = 7.4 +/- 1.8 pg/ml) significantly higher concentrations of IL-8 were detected in the CSF of infants exposed to clinical chorioamnionitis (1,854 +/- 878 pg/ml; p = 0.001) and maternal/fetal inflammation (1,754 +/- 787 pg/ml; p = 0.001) and of IL-6 in infants with maternal/fetal inflammation (47.6 +/- 45.1 pg/ml; p = 0.01). CONCLUSIONS: These results indicate that infants exposed to clinical chorioamnionitis, or inflammation in utero, experience at least a transient elevation in inflammatory cytokines in CSF.

Chorioamnionitis↗

PubMed2006

Variability in cerebral oxygen delivery is reduced in premature neonates exposed to chorioamnionitis.

Premature infants exposed to chorioamnionitis are at increased risk for periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH), lesions that may result from inflammation and/or fluctuations in cerebral blood flow. The effect of chorioamnionitis on near-infrared spectroscopy (NIRS) measures of cerebral oxygen delivery has not been evaluated previously. Forty-nine infants born at 25-31 6/7 wk gestation underwent NIRS examination on d 1, 2, 3, and 7 of life. Variability in NIRS tracings was analyzed by partitioning each tracing into three components: long-term, intermediate, and short-term variability; the latter two components were analyzed. Chorioamnionitis-exposed infants manifest reduced intermediate variability in cerebral oxygenated and deoxygenated Hb but not total Hb. Infants with severe IVH/PVL had the lowest intermediate variability on d 1. Short-term variability was similar between chorioamnionitis-exposed and unexposed infants, and between infants with versus without severe IVH or PVL. We conclude that intermediate-term variability in NIRS cerebral oxygen delivery is reduced in chorioamnionitis-exposed infants. We speculate that intermediate variability represents the important time frame for evaluating the pathogenesis of perinatal brain injury. Further studies are needed to determine how these findings relate to cerebral blood flow autoregulation and oxygen utilization in premature infants.

Brain↗

PubMed2004

Spleen depletion in neonatal sepsis and chorioamnionitis.

Neonatal sepsis and chorioamnionitis induce morphologic modifications and shrinkage of the thymus. We show fetal and neonatal morphologic modifications of the spleen in the same autopsy subjects as previously used to describe thymus shrinkage, including 10 preterm or full-term neonates who died of proven sepsis within 48 hours after birth and 20 fetuses spontaneously aborted because of extensive ascending chorioamnionitis. Control subjects included 10 fetuses from induced termination of pregnancy and 10 neonates who died suddenly during the perinatal period without evidence of chorioamnionitis. Spleen cell populations were studied by means of immunohistochemical analysis. Neonatal sepsis occurred with severe spleen depletion, involving both B and T lymphocytes (P < .001). Fetuses with chorioamnionitis also showed spleen cell depletion. These observations, to our knowledge not described before, indicate that preterm and term neonates show an inflammatory reaction similar to that of adult patients and that severe chorioamnionitis is associated with a nonspecific inflammatory response comparable to that of sepsis.

Antigens, CD20↗

PubMed2002

Chorioamnionitis: elevated interleukin-6 and interleukin-8 concentrations in the lower uterine segment.

AIMS: To determine interleukin (IL)-6 and IL-8 concentrations in the lower uterine segment in patients with chorioamnionitis compared to those without. METHODS: Biopsy specimens from the lower uterine segment of 33 patients with chorioamnionitis were matched to specimens of 33 patients without. The biopsies had been taken during cesarean section. The concentrations of IL-6 and IL-8 in protein extracts of these specimens were determined by enzyme linked immunosorbent assays. RESULTS: Compared to the controls patients with chorioamnionitis showed significantly lower gestational age and higher parity, and were more likely to receive fenoterol or betamethasone. In the chorioamnionitis group the median IL-6 concentrations were higher than in the controls (61.5 and 19.4 pg/mg protein, respectively [p < 0.01]). The same applies to the median IL-8 concentrations (162.3 and 13.4 pg/mg protein, respectively [p < 0.001]). CONCLUSIONS: To our knowledge this is the first study which could clearly demonstrate significantly increased IL-6 and IL-8 levels in the lower uterine segment of patients with chorioamnionitis. Increased concentrations of pro-inflammatory cytokines may play a pivotal role in cervical softening and dilatation during chorioamniotic infection.

Adult↗

PubMed2006

Tumor necrosis factor-alpha and interleukin-1beta regulate interleukin-8 expression in third trimester decidual cells: implications for the genesis of chorioamnionitis.

Chorioamnionitis is associated with intense neutrophil infiltration of the decidua. We therefore determined whether chorioamnionitis enhances decidual interleukin-8 (IL-8) expression and examined cytokine-regulated decidual IL-8 expression. Decidua from chorioamnionitis-complicated pregnancies, but not term controls, displayed marked IL-8 immunohistochemical staining and a dense neutrophil infiltrate. Reverse transcriptase-polymerase chain reaction of microdissected decidual cells identified IL-8 mRNA, confirming decidual synthesis of IL-8. Confluent leukocyte-free term decidual cells were primed with 10(-8) mol/L estradiol (E2) or E2 + 10(-7) mol/L medroxyprogesterone acetate to mimic the steroidal milieu of pregnancy. Compared with cultures maintained in E2 alone, E2 + medroxyprogesterone acetate neither significantly affected IL-8 levels nor altered the response to the cytokines. The addition of 1.0 ng/ml tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1beta) increased IL-8 secretion levels by 236.6 +/- 51.4- and 1062.6 +/- 254.3-fold, respectively (n = 8, mean +/- SEM, P < 0.05), as measured by enzyme-linked immunosorbent assay. Concentration-response studies revealed that 0.01 ng/ml TNF-alpha and IL-1beta elevated IL-8 output by 10- and 100-fold, respectively. Western blotting confirmed these results, and quantitative reverse transcriptase-polymerase chain reaction demonstrated parallel changes in mRNA levels. In conclusion, IL-8 is strongly expressed in term decidua during chorioamnionitis, and TNF-alpha and IL-1beta enhance IL-8 expression in term decidual cells, suggesting that these cytokines are important regulators of chorioamnionitis-related decidual neutrophil infiltration.

Cells, Cultured↗

PubMed1992

Chorioamnionitis: a harbinger of dystocia.

The impact of chorioamnionitis on the course of labor is controversial. Some clinicians believe the infection has stimulatory effects, whereas others suspect inhibitory influences. Two hundred sixty-six pregnancies with chorioamnionitis requiring labor stimulation with oxytocin were matched to uninfected women for maternal age, race, parity, gestational age, oxytocin dosage regimen, indication for labor stimulation, type of labor stimulation, cervical dilatation at initiation of oxytocin, and time for rupture of membranes to initiation of labor stimulation. Chorioamnionitis diagnosed before oxytocin infusion was associated with shorter oxytocin initiation-to-delivery intervals (4.3 versus 5.6 hours; P = .04) and had no significant impact on the cesarean rate compared with matched controls. In contrast, pregnancies complicated by chorioamnionitis detected late in labor were associated with markedly longer oxytocin initiation-to-delivery intervals (12.6 versus 7.9 hours; P less than .0001) and a fourfold increase in cesarean for dystocia compared with matched controls (40 versus 10%; P less than .0001). Thus, the impact of chorioamnionitis on the course of labor can be divided into two clinical presentations. That diagnosed before labor stimulation does not increase the use of cesarean, whereas that diagnosed after oxytocin stimulation may be a sign of abnormal labor, as it was associated with a marked increase in abdominal delivery for dystocia.

Adult↗

PubMed1992

Clinical chorioamnionitis is not predicted by umbilical artery Doppler velocimetry in patients with premature rupture of membranes.

Chorioamnionitis substantially increases fetal and neonatal morbidity. Infants born to women with chorioamnionitis have a fourfold increase in neonatal morbidity. If this condition could be predicted before the clinical manifestation and thereby treated earlier, an improved perinatal outcome might reasonably be expected. Based on the in vitro model of bacteria-induced vasoconstriction and pulmonary hypertension noted in sheep and lambs after exposure to the spent medium of a bacterial culture, we theorized that infected amniotic fluid may produce vasospasm of umbilical and placental vessels, reduce fetal perfusion, and increase perinatal asphyxia, morbidity, and mortality. Umbilical vessel vasospasm may be detected by measuring the systolic-diastolic ratio (S/D) of the umbilical artery. Continuous Doppler flow studies of the umbilical artery S/D were performed prospectively on 51 patients with premature rupture of membranes who were not in labor. The most recent test, done within 1 day of delivery, was compared with pregnancy outcome. Ten subjects developed clinical chorioamnionitis, of whom none had an abnormal S/D. Six of 41 women without clinical chorioamnionitis had abnormal S/Ds. These data do not support the use of Doppler measurement of the S/D as a predictor of clinical chorioamnionitis.

Apgar Score↗

PubMedDate not supplied

Regional anesthesia in women with chorioamnionitis.

BACKGROUND AND OBJECTIVES: Controversy regarding the use of regional anesthesia in parturients with chorioamnionitis stems from concern that, in bacteremic patients, anesthetic technique may result in infectious complications because of "seeding" of the epidural or subarachnoid space. This study attempts to evaluate the outcome of the parturient with chorioamnionitis based on anesthetic technique. METHODS: Data on chorioamnionitis was collected by review of all obstetric deliveries over a 1-year period with respect to type of anesthetic administered, blood culture results, antibiotic administration, and outcome. RESULTS: Three hundred nineteen women with chorioamnionitis were identified from a total of 10,047 deliveries over a 1-year period. Bacteremia was found in eight of these patients, three of whom received epidural anesthesia. None had received antibiotics before induction of anesthesia. No infectious complications related to anesthetic technique were found. Mean temperature and leukocyte counts were not significantly different between bacteremic and nonbacteremic groups. CONCLUSIONS: Although the total number of patients in this study is small, there is no evidence that regional anesthesia was detrimental to patients with chorioamnionitis. Factors such as leukocyte count and temperature elevation may not be predictive in identifying the bacteremic subgroup of patients.

Adult↗

PubMed2005

The significance of C-reactive protein in the diagnosis of fetal tachycardia and therapy of chorioamnionitis.

BACKGROUND: [corrected] Pregnant woman with fetal tachycardia have a risk of chorioamnionitis as cause of tachycardia. Different studies have supported or refuted the use of C-reactive protein (CRP) to diagnose chorioamnionitis. The goal of this study was to evaluate serial serum CRP levels for diagnosis of chorioamnionitis. METHODS: The study included 60 woman with chorioamnionitis confirmed after measuring the levels of CRP. Patients were monitored by CRP determination, white blood cell (WBC) count, maternal temperature, maternal and fetal heart rate. RESULTS: Elevated CRP level was present in 93.33% of cases. Fetal tachycardia was present in 91,67 cases, all associated with elevated CRP level. Increased WBC count was present in 63.33%. A statistically significant difference was found in the level of CRP in pregnant women with increased WBC count compared with those without (p < 0.01). CONCLUSION: Elevated C-reactive protein levels were more sensitive than other standard laboratory or clinical tests in predicting chorioamnionitis. Also, recent reports indicate that serial CRP levels during this interval may be useful for monitoring antibiotic treatment.

Adult↗

PubMed1991

The role of chorioamnionitis and prostaglandins in preterm labor.

Spontaneous preterm labor remains a significant cause of high morbidity and mortality in the newborn. Chorioamnionitis with an associated rise in prostaglandins (PGs) is thought to be one of the factors responsible for the onset of preterm labor. In this study, 52 placentas and membranes from gestations of 35 weeks' or fewer were collected. Tissue samples of membranes and placentas were incubated in pseudoamniotic fluid, and the levels of PGs and leukotriene B4 were assayed. Swallowed amniotic fluid aspirated from the infants' stomachs was analyzed for PGs and examined microscopically for the presence of degenerate neutrophilic polymorphonuclear leukocytes (pus cells) and bacterial organisms. Prostaglandins E and F and leukotriene B4 production were significantly higher in the membranes and placentas with chorioamnionitis than in those without. Although the comparison of PG levels in the gastric fluid of infants with and without chorioamnionitis did not reach statistical significance, there was a trend toward higher levels of PGs with chorioamnionitis. Prostaglandin E levels from membranes and placentas and PGF from placentas were significantly elevated in the gastric fluid of infants with pus cells and organisms. These findings support the hypothesis that chorioamnionitis may initiate preterm labor.

Chorioamnionitis↗